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Regionally distinct trophoblast regulate barrier function and invasion in the human placenta

The human placenta contains two specialized regions: the villous chorion where gases and nutrients are exchanged between maternal and fetal blood, and the smooth chorion (SC) which surrounds more than 70% of the developing fetus but whose cellular composition and function is poorly understood. Here,...

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Autores principales: Marsh, Bryan, Zhou, Yan, Kapidzic, Mirhan, Fisher, Susan, Blelloch, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323019/
https://www.ncbi.nlm.nih.gov/pubmed/35796428
http://dx.doi.org/10.7554/eLife.78829
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author Marsh, Bryan
Zhou, Yan
Kapidzic, Mirhan
Fisher, Susan
Blelloch, Robert
author_facet Marsh, Bryan
Zhou, Yan
Kapidzic, Mirhan
Fisher, Susan
Blelloch, Robert
author_sort Marsh, Bryan
collection PubMed
description The human placenta contains two specialized regions: the villous chorion where gases and nutrients are exchanged between maternal and fetal blood, and the smooth chorion (SC) which surrounds more than 70% of the developing fetus but whose cellular composition and function is poorly understood. Here, we use single cell RNA-sequencing to compare the cell types and molecular programs between these two regions in the second trimester human placenta. Each region consists of progenitor cytotrophoblasts (CTBs) and extravillous trophoblasts (EVTs) with similar gene expression programs. While CTBs in the villous chorion differentiate into syncytiotrophoblasts, they take an alternative trajectory in the SC producing a previously unknown CTB population which we term SC-specific CTBs (SC-CTBs). Marked by expression of region-specific cytokeratins, the SC-CTBs form a stratified epithelium above a basal layer of progenitor CTBs. They express epidermal and metabolic transcriptional programs consistent with a primary role in defense against physical stress and pathogens. Additionally, we show that SC-CTBs closely associate with EVTs and secrete factors that inhibit the migration of the EVTs. This restriction of EVT migration is in striking contrast to the villous region where EVTs migrate away from the chorion and invade deeply into the decidua. Together, these findings greatly expand our understanding of CTB differentiation in these distinct regions of the human placenta. This knowledge has broad implications for studies of the development, functions, and diseases of the human placenta.
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spelling pubmed-93230192022-07-27 Regionally distinct trophoblast regulate barrier function and invasion in the human placenta Marsh, Bryan Zhou, Yan Kapidzic, Mirhan Fisher, Susan Blelloch, Robert eLife Developmental Biology The human placenta contains two specialized regions: the villous chorion where gases and nutrients are exchanged between maternal and fetal blood, and the smooth chorion (SC) which surrounds more than 70% of the developing fetus but whose cellular composition and function is poorly understood. Here, we use single cell RNA-sequencing to compare the cell types and molecular programs between these two regions in the second trimester human placenta. Each region consists of progenitor cytotrophoblasts (CTBs) and extravillous trophoblasts (EVTs) with similar gene expression programs. While CTBs in the villous chorion differentiate into syncytiotrophoblasts, they take an alternative trajectory in the SC producing a previously unknown CTB population which we term SC-specific CTBs (SC-CTBs). Marked by expression of region-specific cytokeratins, the SC-CTBs form a stratified epithelium above a basal layer of progenitor CTBs. They express epidermal and metabolic transcriptional programs consistent with a primary role in defense against physical stress and pathogens. Additionally, we show that SC-CTBs closely associate with EVTs and secrete factors that inhibit the migration of the EVTs. This restriction of EVT migration is in striking contrast to the villous region where EVTs migrate away from the chorion and invade deeply into the decidua. Together, these findings greatly expand our understanding of CTB differentiation in these distinct regions of the human placenta. This knowledge has broad implications for studies of the development, functions, and diseases of the human placenta. eLife Sciences Publications, Ltd 2022-07-07 /pmc/articles/PMC9323019/ /pubmed/35796428 http://dx.doi.org/10.7554/eLife.78829 Text en © 2022, Marsh et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Marsh, Bryan
Zhou, Yan
Kapidzic, Mirhan
Fisher, Susan
Blelloch, Robert
Regionally distinct trophoblast regulate barrier function and invasion in the human placenta
title Regionally distinct trophoblast regulate barrier function and invasion in the human placenta
title_full Regionally distinct trophoblast regulate barrier function and invasion in the human placenta
title_fullStr Regionally distinct trophoblast regulate barrier function and invasion in the human placenta
title_full_unstemmed Regionally distinct trophoblast regulate barrier function and invasion in the human placenta
title_short Regionally distinct trophoblast regulate barrier function and invasion in the human placenta
title_sort regionally distinct trophoblast regulate barrier function and invasion in the human placenta
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323019/
https://www.ncbi.nlm.nih.gov/pubmed/35796428
http://dx.doi.org/10.7554/eLife.78829
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